Our studies are directed primarily toward elucidating the mechanism of action of compounds which modulate gene action in murine virus-induced erythroleukemia cells. We continue to investigate the interaction of biological response modifiers, since it is not understood how DMSO or a variety of unrelated compounds act to trigger the program of erythroid differentiation. What has become clear from our studies is that the translational controls in differentiating FL cells vary from those that regulate normal erythroid cells. In lysates of uninduced FL cells, protein synthesis is unaffected by the omission or addition of either hemin or the hemin-regulated inhibitor, and translation is regulated by hemin-independent controls. Induction does not result in a switch to hemin-dependent translational controls such as those which regulate translation in normal erythroid cells. A hemin-independent inhibitor of globin synthesis present in lysates of uninduced cells cannot be detected in cells which are induced. A further finding was that the differentiating cells had become sensitive to the inhibitor from lysates of their uninduced counterparts. The failure of hemin to stimulate protein synthesis in FL cells may result from either the inability of a translational inhibitor to respond to hemin or the failure of a hemin-dependent protein kinase to affect the function of initiation factor eIF-2. Studies on the erythroleukemia cell lines designated FLvac, which are dually infected with vaccinia virus, are also in progress. These persistently infected cells show a marked decrease in tumorigenicity, but respond to induction with DMSO. Non-producer cells remain resistant to challenge with vaccinia virus. The possibility that the vaccinia genome may be integrated in such cells is under study.